Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) have traditionally been used to decrease serum cholesterol levels and to reduce morbidity and mortality associated with cardiovascular disease in patients with hyperlipidemia. Animal and human studies also suggest that HMG-coenzyme A reductase inhibitors may increase bone formation and bone mineral density. In humans, an increase in bone mineral density can decrease the risk of fractures, especially in patients with osteoporosis.
By analyzing 28 studies involving use of HMGcoA reductase inhibitors or other anti-lipidemic agents in more than 100,000 patients, researchers have concluded that those patients given the HMGcoA inhibitors were 0.76 times as likely to develop strokes as those in the control groups. The stroke rate in patients given fibrates, resins or dietary intervention did not significantly differ from the control groups.
In clinical trials, all doses of colesevelam were generally well tolerated. Colesevelam is not absorbed in the digestive tract, reducing the potential for systemic adverse side effects.
Bile acids are formed from cholesterol in a series of reactions regulated by the enzyme 7-alpha- hydroxylase. During normal digestion, bile acids are secreted into the intestine. A major portion of bile acids are then absorbed from the intestinal tract and returned to the liver via the enterohepatic circulation.
Epidemiological studies have established that elevated levels of total cholesterol (total-C), LDL-cholesterol (LDL-C), and apolipo-protein B (Apo B), as well as decreased levels of HDL-cholesterol (HDL-C), are associated with an increased risk of atherosclerosis and cardiovascular-related mortality. Furthermore, it has been documented through numerous trials that aggressive reduction of lipid levels can significantly reduce the risk of cardiovascular disease.